Extension of life-span with superoxide dismutase/catalase mimetics.

@article{Melov2000ExtensionOL,
  title={Extension of life-span with superoxide dismutase/catalase mimetics.},
  author={Simon Melov and J. Ravenscroft and S. Malik and Matthew S Gill and Don W. Walker and Peter E Clayton and Douglas C. Wallace and Bernard Malfroy and Susan R. Doctrow and Gordon J. Lithgow},
  journal={Science},
  year={2000},
  volume={289 5484},
  pages={
          1567-9
        }
}
We tested the theory that reactive oxygen species cause aging. We augmented the natural antioxidant systems of Caenorhabditis elegans with small synthetic superoxide dismutase/catalase mimetics. Treatment of wild-type worms increased their mean life-span by a mean of 44 percent, and treatment of prematurely aging worms resulted in normalization of their life-span (a 67 percent increase). It appears that oxidative stress is a major determinant of life-span and that it can be counteracted by… Expand
View on PubMed
morelife.org
875 Citations
Highly Influential Citations
12
Background Citations
249
Methods Citations
10
Results Citations
20

875 Citations

Citation Type

Citation Type

Effects of superoxide dismutase/catalase mimetics on life span and oxidative stress resistance in the housefly, Musca domestica.
TLDR
The effect of these SOD/catalase mimetics on the life span of animals seem to be species-specific. Expand
Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria
TLDR
Transgenic mice that overexpress human catalase localized to the peroxisome, the nucleus, or mitochondria were generated and the importance of mitochondria as a source of radicals was reinforced. Expand
Superoxide dismutase mimetics elevate superoxide dismutase activity in vivo but do not retard aging in the nematode Caenorhabditis elegans.
TLDR
An elevation of SOD activity levels sufficient to increase life span when it is limited by superoxide generators does not retard aging in the absence ofsuperoxide generators, which suggests that C. elegans life span is not normally limited by levels of superoxide and its derivatives. Expand
Oxidative stress in Caenorhabditis elegans: protective effects of superoxide dismutase/catalase mimetics
TLDR
The lifespan of Caenorhabditis elegans can be extended by the administration of synthetic superoxide dismutase/catalase mimetics without any effects on development or fertility and the mimetics confer resistance to the oxidative stress‐inducing agent, paraquat and to thermal stress. Expand
Life Span and Oxidative Stress in Nematode
TLDR
This review focuses on the genetics of select long-lived and short-lived mutants of C. elegans that have proven useful in revealing the relationships that exist between oxidative stress and life span. Expand
Mitochondrial respiration and reactive oxygen species in C. elegans
TLDR
Several mutant strains have been identified that indicate that mitochondrial function is a major factor affecting the organism's lifespan, and taken as a group, these mutant strains indicate that metabolic rate, per se, only affects longevity indirectly. Expand
Effect of superoxide dismutase deficiency on the life span of the yeast Saccharomyces cerevisiae. An oxygen-independent role of Cu,Zn-superoxide dismutase.
TLDR
Effects of the absence of Cu,Zn-superoxide dismutase (CuZnSOD) on the replicative life span of the yeast Saccharomyces cerevisiae and the rate of cell divisions were found to be similar under the atmosphere of air and under hypoxic and anoxic conditions. Expand
Nitrosative Stress in Aging - Its Importance and Biological Implications in NF-κB Signaling
The free radical theory of aging is supported by the findings that overex- pression of CuZn superoxide dismutase (SOD) and catalase or the enhancement of reductive capacity by overexpression of… Expand
No increase in lifespan in Caenorhabditis elegans upon treatment with the superoxide dismutase mimetic EUK-8.
TLDR
It is concluded that extension of C. elegans lifespan by EUK-8 may only occur under very particular culture conditions and that dose-dependent reduction of lifespan and fertility is seen. Expand
Effects of nutritional components on stress response and aging in the nematode Caenorhabditis elegans
TLDR
It was assessed in this work that adaptation mechanisms via interruption of the insulin signaling pathways and activation of sirtuin 2.1 induced by mild ROS stress can lead to an increase in life span. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 21 REFERENCES
Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster.
TLDR
A study of the effects of simultaneous overexpression of copper-zinc superoxide dismutase and catalase provides direct support for the free radical hypothesis of aging. Expand
Oxidative stress and ageing in Caenorhabditis elegans.
TLDR
The results clearly show that oxidative stress resistance and potential life span are correlated in this organism, and they suggest that the natural product of age-1 either directly or indirectly downregulates the activities of several other genes as a function of age. Expand
EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology.
TLDR
The effects of EUK-134 on several indices of oxidative stress and neuropathology produced in the rat limbic system as a result of seizure activity elicited by systemic kainic acid (KA) administration support the hypothesis that kainate-induced excitotoxicity is caused, at least in part, by the action of reactive oxygen species. Expand
Aging and resistance to oxidative damage in Caenorhabditis elegans.
  • P. L. Larsen
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1993
TLDR
Results support the free radical theory of aging by suggesting that the increased resistance to oxidative stress may be among the causes of increased longevity in both strain TJ401 and in the dauer larva. Expand
A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes
TLDR
The results indicate that mev-1 governs the rate of ageing by modulating the cellular response to oxidative stress, which may cause an indirect increase in superoxide levels, which in turn leads to oxygen hypersensitivity and premature ageing. Expand
Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons
TLDR
Elevated resistance to oxidative stress suggests that the lifespan extension observed in these flies is due to enhanced RO metabolism, and results show that SOD activity in motorneurons is an important factor in ageing and lifespan determination in Drosophila. Expand
A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase
Reactive oxygen species (ROS) have been implicated in a wide range of degenerative processes including amyotrophic lateral sclerosis, ischemic heart disease, Alzheimer disease, Parkinson disease and… Expand
Synthetic combined superoxide dismutase/catalase mimetics are protective as a delayed treatment in a rat stroke model: a key role for reactive oxygen species in ischemic brain injury.
TLDR
The enhanced activity of EUK-134 suggests that, in particular, hydrogen peroxide contributes significantly to this injury, and suggests that synthetic SOD/catalase mimetics might serve as novel, multifunctional therapeutic agents for stroke. Expand
A methyl viologen-sensitive mutant of the nematode Caenorhabditis elegans.
TLDR
It is suggested that oxygen radicals may be involved in the normal aging mechanism in C. elegans and this mutant was also hypersensitive to oxygen. Expand
The p66shc adaptor protein controls oxidative stress response and life span in mammals
TLDR
It is proposed that p66shc is part of a signal transduction pathway that regulates stress apoptotic responses and life span in mammals. Expand
...
1
2
3
...